Therapeutic nanovaccines sensitize EBV-associated tumors to checkpoint blockade therapy

作者：Liu, Hong; Chen, Haolin; Liu, Zhijia; Le, Zhicheng; Nie, Tianqi; Qiao, Dongdong; Su, Yan; Mai, Haiqiang; Chen, Yongming; Liu, Lixin

来源：Biomaterials, 2020, 255: 120158.

DOI：10.1016/j.biomaterials.2020.120158

• Checkpoint inhibitor
• Immunotherapy
• Nanovaccine
• Subunit antigen
• Tannic acid
• Tumors

For successful treatment of EBV-associated tumors immune tolerance must be broken. While most studies of EBV-associated tumor vaccines have focused on augmenting tumor-specific effector T cells, the effects of these vaccines on the immune-suppressive tumor microenvironment have not been investigated. Here, we describe the manufacture of a nanovaccine using tannic acid (TA) and a newly constructed protein antigen for EBV-associated tumors with interferon-alpha (IFN-alpha) or CpG as adjuvants. TA as a biocompatible material from plant self-assembles with antigens and adjuvants via hydrogen bonding to form well-defined nanoparticulate vaccines by flash nanocomplexation, a scalable yet controllable technique. By targeting lymph nodes, the nanovaccine co-loaded with CpG adjuvant induces strong immune activation and exhibits efficient inhibition tumorigenesis. Moreover, the nanovaccine combining with anti-PD-L1 results a marked decrease in tumor size and prolonged survival of tumor-bearing mice by decreasing infiltration of regulatory T cells to the tumor lesion. This suggests that the nanovaccine can reverse immune checkpoint inhibitor resistance by remodeling the tumor microenvironment. Thus, this study shows a promising strategy for treatment of EBV-positive tumors in patients.

• 单位
  中山大学